Why does restless sleep predict Parkinson's disease?

Rapid eye movement sleep behavior disorder is associated with an increased risk of developing Parkinson's disease. For the first time, researchers demonstrate that inflammation may play a key role.

A new study has uncovered links between Parkinson's and RBD.

Rapid eye movement (REM) sleep behavior disorder (RBD) is linked with vivid and often frightening dreams combined with nocturnal motor activity. In other words, people with the condition act out their dreams.

Dreaming occurs during REM sleep. In this sleep phase, our bodies are effectively paralyzed and our muscles remain relaxed; this prevents us from thrashing around.

Individuals with RBD, however, can experience violent arm and leg movements and even shout during their dreams. This is referred to as dream-enacting behavior.

Episodes might only occur every so often, or they can appear multiple times during one night. RBD generally appears in mid- to later life and tends to get worse over time. The condition can be distressing and cause injury to the individual and their sleeping partner.

RBD and Parkinson's disease

Researchers have found that RBD is linked to an increased risk of developing Parkinson's disease later in life.

The condition can precede Parkinson's disease and other dementias by half a century. In fact, most people with RBD will go on to develop Parkinson's, Lewy body dementia, or multiple system atrophy. But why this relationship exists is unclear.

Recently, researchers from Aarhus University in Denmark set out to investigate this interaction in more detail. Of particular interest to the researchers was the role of neuroinflammation. Their findings are published this week in The Lancet Neurology.

Parkinson's disease is caused by the death of dopamine-producing neurons in a part of the striatum called the substantia nigra. As dopamine levels are slowly reduced, the characteristic motor symptoms of Parkinson's disease appear, including rigid muscles, tremor, slow movement, and changes in speech.

In Parkinson's disease and similar conditions, inflammation in the brain has also been observed. In particular, there is an activation of microglia, which are a type of macrophage and a major player in the central nervous system's immune response. They are heavily involved in neuroinflammation.

Influencing this inflammatory response is currently being investigated as a potential route to treatment for Parkinson's disease.

Investigating the role of inflammation

The team wanted to understand whether or not this neuroinflammation might also be occurring in RBD. They carried out PET scans on 20 individuals with medically confirmed RBD and compared them with 19 healthy controls. They assessed microglial activation in different regions of the striatum (the substantia nigra, caudate, and putamen). Dopamine neuron function was also assessed.

As expected, they found that in people with RBD, there was increased microglial activation in the substantia nigra and reduced dopaminergic function in the putamen. The authors write:

"In summary, we have shown that raised microglial activation in the substantia nigra and reduced presynaptic nigrostriatal dopaminergic function can be detected in patients with RBD [...] This result implies that neuroinflammation and dopaminergic deficit occur in patients with RBD."

Further studies will be needed to confirm these findings; the study involved only a relatively small number of subjects. The researchers also want to follow the people from the study to observe whether or not Parkinson's does develop in those with RBD.

But if the results are replicated, it may offer a new potential route to treating RBD and possibly slowing the onset of Parkinson's. As the authors write, "Modulation of microglial activation could provide a potential therapeutic strategy for slowing disease progression, particularly in its earliest stages."

The study adds to the evidence that neuroinflammation is a factor in both Parkinson's disease and RBD. In the future, these findings might help to catch the disease earlier and potentially offer a route to new treatments.

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